DYR1B_MOUSE
ID DYR1B_MOUSE Reviewed; 629 AA.
AC Q9Z188; Q3UFR5; Q70UR5; Q9EPM2;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 3.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Dual specificity tyrosine-phosphorylation-regulated kinase 1B;
DE EC=2.7.12.1 {ECO:0000269|PubMed:12633499};
GN Name=Dyrk1b;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=129/SvJ, and NMRI; TISSUE=Liver, and Testis;
RX PubMed=9918863; DOI=10.1006/bbrc.1998.9967;
RA Leder S., Weber Y., Altafaj X., Estivill X., Joost H.-G., Becker W.;
RT "Cloning and characterization of DYRK1B, a novel member of the DYRK family
RT of protein kinases.";
RL Biochem. Biophys. Res. Commun. 254:474-479(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, CATALYTIC ACTIVITY, AND FUNCTION.
RC STRAIN=NMRI;
RX PubMed=12633499; DOI=10.1042/bj20030182;
RA Leder S., Czajkowska H., Maenz B., De Graaf K., Barthel A., Joost H.-G.,
RA Becker W.;
RT "Alternative splicing variants of dual specificity tyrosine phosphorylated
RT and regulated kinase 1B exhibit distinct patterns of expression and
RT functional properties.";
RL Biochem. J. 372:881-888(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-533 (ISOFORM 2).
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
CC -!- FUNCTION: Dual-specificity kinase which possesses both serine/threonine
CC and tyrosine kinase activities (PubMed:12633499). Plays an essential
CC role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy
CC number maintenance. During DNA damage, mediates transcription silencing
CC in part via phosphorylating and enforcing DSB accumulation of the
CC histone methyltransferase EHMT2. Enhances the transcriptional activity
CC of TCF1/HNF1A and FOXO1. Inhibits epithelial cell migration. Mediates
CC colon carcinoma cell survival in mitogen-poor environments. Inhibits
CC the SHH and WNT1 pathways, thereby enhancing adipogenesis. In addition,
CC promotes expression of the gluconeogenic enzyme glucose-6-phosphatase
CC catalytic subunit 1 (G6PC1). {ECO:0000250|UniProtKB:Q9Y463,
CC ECO:0000269|PubMed:12633499}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC Evidence={ECO:0000269|PubMed:12633499};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.12.1; Evidence={ECO:0000269|PubMed:12633499};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC Evidence={ECO:0000269|PubMed:12633499};
CC -!- ACTIVITY REGULATION: Inhibited by RANBP9. {ECO:0000250}.
CC -!- SUBUNIT: Dimer. Interacts with DCOHM, MAP2K3/MKK3, RANBP9 and
CC TCF1/HNF1A. Part of a complex consisting of RANBP9, RAN, DYRK1B and
CC COPS5. Interacts with DCAF7. Interacts with RNF169.
CC {ECO:0000250|UniProtKB:Q9Y463}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y463}. Nucleus,
CC nucleolus {ECO:0000250|UniProtKB:Q9Y463}. Chromosome
CC {ECO:0000250|UniProtKB:Q9Y463}. Note=Localizes to sites of double-
CC strand breaks (DSBs) following DNA damage.
CC {ECO:0000250|UniProtKB:Q9Y463}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=p69;
CC IsoId=Q9Z188-1; Sequence=Displayed;
CC Name=2; Synonyms=p65;
CC IsoId=Q9Z188-2; Sequence=VSP_022955;
CC Name=3; Synonyms=p75;
CC IsoId=Q9Z188-3; Sequence=VSP_022954;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are broadly expressed.
CC Isoform 3 seems specific for skeletal muscle (at protein level).
CC {ECO:0000269|PubMed:12633499}.
CC -!- DEVELOPMENTAL STAGE: Isoform 1 is present from 14 dpc. Isoform 3 is
CC present from 18 dpc (at protein level). {ECO:0000269|PubMed:12633499}.
CC -!- PTM: Phosphorylated by MAP kinase. Tyrosine phosphorylation may be
CC required for dimerization (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 2]: Inactive. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MNB/DYRK subfamily. {ECO:0000305}.
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DR EMBL; Y18280; CAA77101.2; -; mRNA.
DR EMBL; AJ252172; CAC20675.1; -; Genomic_DNA.
DR EMBL; AJ537610; CAD61290.1; -; mRNA.
DR EMBL; BC019545; AAH19545.1; -; mRNA.
DR EMBL; AK148342; BAE28495.1; -; mRNA.
DR CCDS; CCDS21037.1; -. [Q9Z188-1]
DR CCDS; CCDS57532.1; -. [Q9Z188-2]
DR CCDS; CCDS85251.1; -. [Q9Z188-3]
DR PIR; JG0196; JG0196.
DR RefSeq; NP_001033046.1; NM_001037957.3. [Q9Z188-1]
DR RefSeq; NP_001258299.1; NM_001271370.1. [Q9Z188-3]
DR RefSeq; NP_034222.1; NM_010092.2. [Q9Z188-2]
DR AlphaFoldDB; Q9Z188; -.
DR SMR; Q9Z188; -.
DR BioGRID; 199348; 13.
DR CORUM; Q9Z188; -.
DR ELM; Q9Z188; -.
DR STRING; 10090.ENSMUSP00000083064; -.
DR iPTMnet; Q9Z188; -.
DR PhosphoSitePlus; Q9Z188; -.
DR jPOST; Q9Z188; -.
DR MaxQB; Q9Z188; -.
DR PaxDb; Q9Z188; -.
DR PeptideAtlas; Q9Z188; -.
DR PRIDE; Q9Z188; -.
DR ProteomicsDB; 277655; -. [Q9Z188-1]
DR ProteomicsDB; 277656; -. [Q9Z188-2]
DR ProteomicsDB; 277657; -. [Q9Z188-3]
DR Antibodypedia; 30414; 362 antibodies from 36 providers.
DR DNASU; 13549; -.
DR Ensembl; ENSMUST00000085901; ENSMUSP00000083064; ENSMUSG00000002409. [Q9Z188-1]
DR Ensembl; ENSMUST00000172467; ENSMUSP00000133431; ENSMUSG00000002409. [Q9Z188-3]
DR Ensembl; ENSMUST00000172761; ENSMUSP00000133719; ENSMUSG00000002409. [Q9Z188-2]
DR GeneID; 13549; -.
DR KEGG; mmu:13549; -.
DR UCSC; uc009fxz.2; mouse. [Q9Z188-2]
DR UCSC; uc009fya.2; mouse. [Q9Z188-1]
DR UCSC; uc009fyb.2; mouse. [Q9Z188-3]
DR CTD; 9149; -.
DR MGI; MGI:1330302; Dyrk1b.
DR VEuPathDB; HostDB:ENSMUSG00000002409; -.
DR eggNOG; KOG0667; Eukaryota.
DR GeneTree; ENSGT00940000160345; -.
DR HOGENOM; CLU_000288_5_6_1; -.
DR InParanoid; Q9Z188; -.
DR OMA; GHSTADY; -.
DR OrthoDB; 689446at2759; -.
DR PhylomeDB; Q9Z188; -.
DR TreeFam; TF314624; -.
DR BRENDA; 2.7.12.1; 3474.
DR BioGRID-ORCS; 13549; 4 hits in 78 CRISPR screens.
DR PRO; PR:Q9Z188; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9Z188; protein.
DR Bgee; ENSMUSG00000002409; Expressed in spermatid and 130 other tissues.
DR Genevisible; Q9Z188; MM.
DR GO; GO:0005694; C:chromosome; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI.
DR GO; GO:0060612; P:adipose tissue development; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0007520; P:myoblast fusion; IMP:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:InterPro.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR CDD; cd14226; PKc_DYRK1; 1.
DR InterPro; IPR028318; DYRK1A/B_MNB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR044131; PKc_DYR1A/1B.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24058:SF12; PTHR24058:SF12; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Chromosome; DNA damage; DNA repair;
KW Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..629
FT /note="Dual specificity tyrosine-phosphorylation-regulated
FT kinase 1B"
FT /id="PRO_0000085935"
FT DOMAIN 111..431
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 67..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 380..399
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 436..480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 480..520
FT /note="Interaction with RANBP9"
FT /evidence="ECO:0000250"
FT REGION 496..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 69..86
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 439..480
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 546..586
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 239
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 117..125
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 140
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 190..193
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 63
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 92
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 111
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 129
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 171
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q63470"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 271
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9Y463"
FT MOD_RES 273
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y463"
FT MOD_RES 401
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 624
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT VAR_SEQ 1
FT /note="M -> MLAARPPHWGPHRAPAPRGPSAIPDPGLSGGGSRGAGCEKAPPGRAP
FT APGLTPLRPSEPTM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12633499"
FT /id="VSP_022954"
FT VAR_SEQ 366..405
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:9918863"
FT /id="VSP_022955"
FT CONFLICT 459
FT /note="P -> H (in Ref. 4; BAE28495)"
FT /evidence="ECO:0000305"
FT CONFLICT 531
FT /note="S -> P (in Ref. 4; BAE28495)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 629 AA; 69178 MW; 54FCE6DBD3918D1C CRC64;
MAVPPGHGPF SGFPGPQEHT QVLPDVRLLP RRLPLAFRDA ASAPLRKLSV DLIKTYKHIN
EVYYAKKKRR AQQAPPQDSS TKKEKKVLNH GYDDDNHDYI VRSGERWLER YEIDSLIGKG
SFGQVVKAYD HQTQELVAIK IIKNKKAFLN QAQIELRLLE LMNQHDTEMK YYIVHLKRHF
MFRNHLCLVF ELLSYNLYDL LRNTHFRGVS LNLTRKLAQQ LCTALLFLAT PELSIIHCDL
KPENILLCNP KRSAIKIVDF GSSCQLGQRI YQYIQSRFYR SPEVLLGTPY DLAIDMWSLG
CILVEMHTGE PLFSGSNEVD QMSRIVEVLG IPPAPMLEQA PKARKYFERL PGGGWTLRRT
KELRKDYQGP GTRRLQEVLG VQTGGPGGRR AGEPGHSPAD YLRFQDLVLR MLEYEPAARI
SPLGALQHGF FRRTADEATN TGPAGSSAST SPAPLDTCPS SSTASSISSS GGSSGSSNDN
RAYRYSNRYC GGPGPPITDC EMNSPQVLPS QPLRPWAGGD VPHKTHQAPI SASTLPGTGA
QLPPLPRCLG RPPSPTSPPP PELMDVSLVG SPPDCSPPPP APAPQHPAAS ALRTRMTGGR
PPLPPPDDPA TLGPRLGLHG VPQSTAASS
